The broad objectives of this proposal are: 1) to examine and analyze interacting factors, i.e., mechanical-physical, neurogenic, biogenic, controlling microcirculation. Venular distensibility gradients required to evoke arteriolar and precapillary sphincter response will be further analyzed in mesentery, and the study extended to skeletal (cremaster) muscle, and brain (pial) vasculatures, in rats and gerbils. 2) Explore the nature of the venous-arteriolar response, and correlation will be made of the microvascular diametric changes and local blood flow modifications. 3) An assessment will be made of the influence of selected number of naturally occurring biogenic molecules upon microvascular response to central neural stimulation, in mesentery and skeletal muscle. The manner of the interference with the neurally mediated stimulus by opposite acting chemicals in terms of modification of the level of tone and reactivity of microvessels in smooth muscle will be quantitatively evaluated. 4) The extent of the influence, if any, of other central neural transmitter loci, e.g., nucleus coereleus, on cerebral (pial-cortical) and other tissues microcirculation will be examined. The primary long-term goal of this study is to complete the description of the manner in which vascular and extravascular variables interact in regulating microcirculation in conventional young rats and gerbils, aged rats, and germfree and hypertensive rats. The quantitative assessment of microvascular geometric variables and its changes will be made in anesthetized animals using the image-splitting T.V. microscopy technique developed in this laboratory. Wherever possible, e.g., cremaster muscle, a "tissue micro-tensor" devised in our laboratory will be applied to examine the contribution of environmental forces, stress, strain parameter of supporting tissue. Videotape records and still microcinematography data will be used to secure information for the evaluation of longitudinal stress-strain parameter to the distensibility characteristics of the microvessels. A "diode red cell velocity sensor device" will be be employed to gather information for determining blood flow data.